This application is directed to a formulation for the buccal administration of an active ingredient. Buccal administration (in the pouch of the cheek of the subject) is particularly useful for active ingredients which show poor bioavailability upon administration through other non-parenteral modes. This poor availability can be attributed to low solubility, degradation by enzyme or destruction by acid upon passing through the intestinal tract, or first pass destruction by the liver after absorption from the gastrointestinal tract. Examples of such medicaments include: steroids such as estrogens, e.g. estradiol and derivatives such as the salt and valerate, cypionate or propionate forms; progestins, e.g. progesterone and related compounds, androgens and anabolic steroids; propranolol; thyroid hormones; pH sensitive peptides and small proteins such as insulin and ACTH; physostigmine; scopolamine; verapamil; and gallopamil. It is also possible to administer compounds having good oral bioavailability buccally, but normally such medicaments would be administered orally for convenience.
Buccal administration of estradiol gives an early peak in the blood level followed by decreasing concentration. This tracks the natural occurrence of estradiol in the body, and thus is an improvement over transdermal administration, which provides a relatively constant blood level. Oral administration of estrogens such as estradiol is impractical in view of the destruction of the active ingredient in the liver shortly after absorption from the gastrointestinal tract.
It is necessary for a buccal formulation to remain in contact with the oral mucosa for a time sufficient for absorption of the medicament to be administered. If the formulation falls apart too quickly. the active ingredient is swallowed, and an insufficient amount of medicament is delivered. If the formulation does not fall apart quickly enough, patient compliance difficulties can result, since the patient should not eat or drink while using the buccal formulation. The formulation should be of a small size to avoid discomfort to the patient and it is desirable that as much of the formulation as possible be soluble in saliva so that discomfort in the form of insoluble grit in the mouth can be avoided.